The COSMOS Project (Integrated In Silico Models for the Prediction of Human Repeated Dose Toxicity of COSMetics to Optimise Safety, www.cosmostox.eu) is a unique international collaboration addressing the safety assessment needs of the cosmetics industry without the use of animals. COSMOS is developing an integrated suite of computational workflows including models based on the threshold of toxicological concern (TTC) approach, innovative toxicity prediction strategies based on chemical categories, read-across and quantitative structure activity relationships (QSARs) related to key events in adverse outcome pathways and multi-scale modeling based on physiologically-based pharmacokinetics to predict target organ concentrations and extrapolate from in vitro to in vivo exposure scenarios. The KNIME technology is being used to integrate access to databases and modeling approaches into flexible computational workflows that will be made publicly accessible and provide a transparent method for use in the safety assessment of cosmetics. First results include establishing the COSMOS chemical inventory of cosmetic ingredients and their associated chemical structures; a new dataset for TTC analysis for assessment of the applicability of the TTC approach to cosmetics; developing the COSMOS database for repeated dose toxicity data; as well as KNIME workflows to identify structural rules, fragments and properties associated with particular mechanisms of toxicity.